April 16, 2013

Male circumcision reduces the abundance of bacteria living on the penis and might help explain why circumcision offers men some protection against HIV, according to a study led by the Translational Genomics Research Institute (TGen).

Removing the foreskin caused a significant shift in the bacterial community or microbiome of the penis, according to a study published today by the online journal mBio.

This international collaboration focused on 156 men in Rakai, Uganda – part of the world's largest randomized-controlled trial on male circumcision. Researchers showed that men who were circumcised as part of the study had 33.3 percent less bacteria on their penis than those who remained uncircumcised one year after the study began.

Researchers further showed that the decrease was primarily found in 12 types of bacteria, most of which were intolerant to oxygen.

Past studies have shown that circumcision reduces female-to-male HIV transmission, among other benefits. This study suggests a possible mechanism for HIV protection – the shift in the number and type of bacteria living on the penis. Further studies will have to be done to demonstrate that a change in the penis microbiome can help reduce the risk of HIV transmission, according to the authors.

At the same time, understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, especially for populations with high HIV prevalence and in places where male circumcision is culturally less acceptable, the study says.

"We know that male circumcision can prevent HIV and other diseases in heterosexual men, but it is important to know why," said Dr. Lance Price, the Director of TGen Center for Microbiomics and Human Health and the study's senior author.

"We think that these dramatic changes in the penis microbiome may explain, at least in part, why male circumcision is protective, " said Dr. Price, who is also a Professor of Environmental and Occupational Health in the School of Public Health and Health Services at the George Washington University.

In heterosexual transmission of HIV, the virus on the foreskin needs to reach its target cells, the CD4+ T-cells, which reside primarily in blood or the lymph nodes.

Researchers hypothesize that penis bacteria may facilitate this process in two ways: by both recruiting more HIV target cells to the foreskin and by triggering another set of immune cells, the Langerhans cells, to deliver the virus to susceptible T-cells. Without this trigger, the Langerhans cells will simply destroy the virus.

"Our findings are interesting from two perspectives. From a public health standpoint, we were finally able to detail the bacterial changes associated with male circumcision," said Dr. Cindy Liu, Adjunct Professor at the Pathogen Genomics Division at TGen, and the study's lead author.

"From an ecological perspective, our study shows how phenomena from the macro-world actually scale to the micro level. When you change a macro environment, such as clear cutting a forest, you affect the animals that live there. That's intuitive. Here we show that changing the penis environment affects the microbes that live there as well." said Dr. Liu, who also is a member of the Department of Pathology at the Johns Hopkins School of Medicine.

"Even though disturbances of the microbiome are usually portrayed as negative, such as in colitis and yeast infection after antibiotic use," said Dr. Price, "this may be one place where dramatic changes can be protective."